This application is a U.S. National Stage of International application PCT/IB98/01490, filed Sep. 24, 1998 and published on Apr. 8, 1999 in the English Language.
1. Field of the Invention
The present invention relates to devices that are adapted for implantation within the human body and methods for making such devices. More particularly, the present invention relates to a method for coating such devices and the devices coated thereby, wherein the coating increases the bio-compatibility and the medical usefulness of the device.
2. Description of Related Art
Artificial implantable devices, such as prosthetic devices or artificial eye lenses, have been implanted in humans for many years. For example, an artificial lens can be implanted in the posterior or anterior chamber of the human eye to restore vision of patients, as is done following cataract extraction. The function of the artificial lens, like the natural crystalline lens, is to maintain transparency and refract incidental light to focus the light on the retina for visual acuity.
Implantable artificial lenses, referred to as intraocular lenses ( less than  less than IOLs greater than  greater than ), have been made using many different designs. A common form of intraocular lens includes a central circular lens, frequently with flexible haptic loops radiating from the circumference of the lens to center the lens and maintain the position of the lens within the eye chamber.
The lens and haptic loops have been made from a number of different materials. Presently, polymethylmethacrylate (PMMA) is the most common material used for the lens portion of the IOL. Haptic loops have been made from a variety of materials, including plastics or metals. The haptic loops must be flexible and retain a spring-like quality to properly hold the lens in place without causing discomfort, such as from rubbing or tension on the ocular tissues. However, metal-loop lenses and poorly polished lenses can lead to chafting of the iris and related complications.
The tissues of the anterior segment of the eye and the corneal endothelium are bathed in an aqueous humor containing hydrogen peroxide (H2O2), lipid hydroperoxides and other reactive oxygen species. Natural crystalline lenses are anteriorly covered by a single layer of cuboidal epithelial cells which are highly metabolically active, and natural crystalline lenses that are healthy can tolerate substantial concentrations of such peroxides and lipid hydroperoxides without apparent damage. This ability of the natural lens is attributed to an active glutathione redox cycle. Typical concentrations of hydrogen peroxide in the aqueous humor of a healthy eye are on the order of 20 to 30 xcexcM (micro-moles per liter).
However, the average concentration of peroxides in cataract patients is elevated, typically to about 40 xcexcM. Higher concentrations, such as 50 xcexcM or higher, have been shown to cause significant corneal swelling and a decrease in the glutathione concentration. Concentrations of 50 xcexcM or higher have also been shown to cause damage to DNA, including single strand breaks.
In addition to the foregoing complications, these oxygen derivatives and peroxide compounds are believed to contribute to pathological processes in ageing and systematic diseases, such as diabetes, artherosclerosis, chronic renal failure, inflammation and retinal degenerative diseases. IOLs that are implanted within the eye, for example after cataract extraction, do not have the ability to reduce or stabilize the concentration of these detrimental peroxide compounds. Therefore, the foregoing problems persist when the natural lens is replaced with an IOL. There is also evidence that PMMA lenses cause granulocytes to release significant amounts of oxygen radicals.
As it is discussed above, the anterior cuboidal epithelial cells of the natural crystalline lens which provide the antioxidant protection of the natural lens are usually removed during cataract extraction. However, the equatorial residual epithelial cells of the crystalline lens can spread to the posterior capsule, grow, and cause secondary opacification of the IOL after implantation. Further, a PMMA lens can cause a foreign body reaction accompanied by the formation of giant cells and macrophages on the IOL and acute chronic inflammation of the eye. The interaction between the ocular tissue and the artificial IOL can also be responsible for complications such as post operative inflammation, cell and pigment deposits on the lens, capsule opacification and macular oedema, a swelling of the macula of the retina.
U.S. Pat. No. 5,376,116 by Poler is directed to an intraocular lens device for impeding secondary growth within an eye, such as the growth of epithelial cells. It is disclosed that epithelial cell and protein strand development can be impeded by providing one or more metals and/or a basic salt in the environment or in the construction of the intraocular lens. It is believed that the metal and/or basic salt provide an electrolytic action within the capsule and that cell growth is thereby reduced. The changed pH, temperature and chemical balance that result allegedly reduce or eliminate-the ability of epithelial cells to multiply. When metal coatings are used, complicated schemes are used to produce patterns of at least two different metals on the lens surface. The device may be plated using known techniques and the thickness of the adhered coating is about 316 to 633 nm, as determined by interferometry.
U.S. Pat. No. 4,718,905 by Freeman is directed to a haptic element for an intraocular lens. The longevity of the haptic is enhanced by a bio-compatible and inert ion coating of the polypropylene haptic on the surfaces making tissue contact. The preferred coating elements are nitrogen, carbon, silicon and aluminum and the protective ion coating is applied by ion beam implantation.
Ion beam implantation has significant disadvantages. The implanted ions create a net positive surface charge which can facilitate the formation of free radicals. Further, the ions penetrate the surface of the device to a depth of up to 2 xcexcm. This creates a new structure with decreased flexibility, stability and smoothness. Further, the process occurs at elevated temperatures which can damage the device. The process is also a  less than  less than line of sight greater than  greater than  process which is not readily adaptable to high volume production of devices.
It would be useful to provide a biologically compatible implantable device, such as an intraocular lens that mimics the capacity of the crystalline lens to withstand oxidative stresses and provide a reduction of peroxide compounds in ocular humors, thus preventing cellular disfunction and pathologies resulting from oxidative attack. It would be useful if such a device could be fabricated without sacrificing the desirable physical properties of the device, such as flexibility and smoothness.
In addition to the need for improved IOL devices, there is a need for improved bio-compatibility for other devices. Because oxidative stress (e.g., an increase in peroxide concentration) can create internal disorders, there is a need for minimizing the adverse reaction of polymeric materials implanted into the human body. Such devices can include polymeric bone implants, medical sewing materials, and artificial polymeric vessels. Such devices can also include prosthetic heart devices, which should be resistant to thrombosis. In addition, there is a need for improved coatings for ophthalmic devices such as ophthalmic lenses and contact lenses, which are placed in contact with the human eye.
According to one aspect of the present invention, a device is provided which is adapted to be implanted within a human body wherein the device includes an outer surface having a coating deposited on at least a portion thereof by magnetron sputtering. Preferably, the coating has an average thickness of less than about 1 xcexcm, more preferably less than about 500 angstroms. The coating can preferably include an element selected from the group consisting of platinum, palladium, manganese, nickel, gold, silver, rhodium, rhenium, cobalt, iridium, titanium, zirconium, niobium, tantalum, vanadium, aluminum, carbon, silicon, selenium, tin, boron, chromium, germanium, phosphorus, yttrium, hafnium, molybdenum, lanthanum, scandium, gadolinium, europium, terbium, neodymium, samarium, dysprosium, gallium, ytterbium, lutetium, erbium, thulium, calcium, magnesium, barium, cerium, zinc and indium, and compounds and combinations and alloys thereof, as well as compounds of nitrogen and oxygen. For some applications, copper and iron may also be useful. In a more preferred embodiment, the coating comprises platinum or an alloy thereof. In one embodiment, magnetron sputtering is applied for coating the outer surface of ophthalmic and implantable devices. Magnetron sputtering deposits the coating at much lower substrate temperatures (e.g., 20-50xc2x0 C.), employing a super-cool sputtering processing method. The result is shorter batch processing times, combined with much better quality coatings applicable to organic/polymeric optical materials. Magnetron sputtering has distinct advantages over other vacuum technologies of coatings, for example electronic-beam, gun-evaporation, thermal evaporation, etc., since Magnetron-aided coating processing excludes the thermal load to the substrate. The device can be a prosthetic device or, in a preferred embodiment, can be an intraocular lens adapted to be implanted within a human eye. It should be understood that the term implantable devices can include partially implanted devices such as ophthalmic lenses and contact lenses for correcting vision.
According to another aspect of the present invention, an intraocular lens structure is provided. The intraocular lens includes a lens body adapted to be implanted within an eye and means for supporting the lens body within the eye wherein the supporting means includes at least one projection attached to the lens body wherein the projection has a first coating deposited thereon by magnetron sputtering. Preferably, the supporting means includes a plurality of haptic elements emanating from a circumference of the lens. In one embodiment, the lens body comprises polymethylmethacrylate. The lens structure can further include a second coating on the lens body wherein the second coating has an average thickness of less than about 500 angstrom. Preferably, the second coating has substantially the same composition as the first coating. Further, the second coating can be selected to reduce the transmission of ultraviolet light through the lens body. In a preferred embodiment, the projections are fabricated from polypropylene. The coating can optionally have a carbon film between the coating and the device to enhance the adherence of the coatings.
According to another aspect of the present invention, a method for treating an intraocular lens structure is provided. The method includes the step of magnetron sputtering a first metal onto the haptics to form a first metal coating on the haptics. Preferably, the coating has an average thickness of less than about 1 xcexcm, more preferably less than about 500 angstroms.
The present invention also provides a method for decreasing the oxygen radical content and for reducing ocular inflammation. The method also reduces the levels of hydroperoxide compounds in the anterior chamber of an eye after implantation of an artificial intraocular lens. The method may also decrease the level of aldehyde and the products of oxidative modification of biomolecules in the anterior chamber. The method includes the steps of implanting an intraocular lens structure which includes a metal coating thereon having average thickness of less than about 500 angstroms, wherein the metabolically active coating includes a metabolically active element selected from the group consisting of platinum, palladium, manganese, nickel, gold, silver, rhodium, rhenium, cobalt, iridium, titanium, zirconium, niobium, tantalum, vanadium, aluminum, carbon, silicon, selenium, tin, boron, chromium, germanium, phosphorus, yttrium, hafnium, molybdenum, lanthanum, scandium, gadolinium, europium, terbium, neodymium, samarium, dysprosium, gallium, ytterbium, lutetium, erbium, thulium, compounds of nitrogen and oxygen, and indium, and compounds, combinations and alloys thereof.